Immunotherapy + Chemotherapy for Lung Cancer

(POSEIDON Trial)

Not currently recruiting at 175 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids

Disqualifiers: Autoimmune disorders, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: Approximately 25 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with metastatic non-small-cell lung cancer (NSCLC). Researchers aim to determine if combining immunotherapy drugs, such as durvalumab (Imfinzi) and tremelimumab, with standard chemotherapy is more effective than chemotherapy alone. The trial includes three groups: one receives both immunotherapy and chemotherapy, another receives durvalumab with chemotherapy, and the last receives only chemotherapy. Suitable candidates have advanced NSCLC without certain genetic mutations (EGFR or ALK) and have not received prior treatment for this cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that durvalumab, whether used alone or with tremelimumab, is generally safe for patients with various types of cancer. When used by itself, durvalumab is well-tolerated and does not cause unexpected side effects in patients with advanced lung cancer.

When combined with tremelimumab, durvalumab also maintains an acceptable safety profile. In one study, about 1.3% of patients experienced serious lung inflammation, known as pneumonitis. Most cases were mild, but a few were more serious.

These findings suggest that both treatments are manageable for most patients. However, as with any medical treatment, possible side effects exist, and participants should be aware of them. It is important to consult healthcare professionals to understand the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine immunotherapy with traditional chemotherapy to enhance the fight against lung cancer. Durvalumab and tremelimumab are unique because they work by ramping up the immune system to specifically target and destroy cancer cells, unlike standard chemotherapy that attacks all rapidly dividing cells. This combination approach has the potential to not only improve survival rates but also reduce the recurrence of cancer, offering a more targeted and effective treatment option.

What evidence suggests that this trial's treatments could be effective for metastatic non-small-cell lung cancer?

In this trial, participants will be assigned to different treatment arms to evaluate the effectiveness of various therapies for lung cancer. Research has shown that combining the drugs durvalumab and tremelimumab with chemotherapy, as in Treatment Arm 1, can extend the lives of lung cancer patients. Specifically, the POSEIDON study demonstrated that this combination significantly improved both overall survival and progression-free survival compared to chemotherapy alone. Treatment Arm 2 involves adding durvalumab to chemotherapy, which also extended progression-free survival compared to traditional treatments. Reports from patients and clinical data support these findings, indicating that both treatment options are promising for treating advanced non-small cell lung cancer. Overall, these treatments effectively improve outcomes for patients with this type of lung cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Xiaojin Shi, M.D., MSc

Principal Investigator

One MedImmune Way, Gaithersburg, Maryland 20878, United States

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV non-small cell lung cancer (NSCLC) without certain gene mutations. Participants should be in good physical condition, not have had previous systemic therapy for metastatic NSCLC, and must not have autoimmune diseases, mixed lung cancers, brain metastases unless stable and off steroids, or active infections like TB or hepatitis.

Inclusion Criteria

My lung cancer is confirmed to be at stage IV.

I have never received immune therapy, except for cancer vaccines.

My tumor's PD-L1 status has been confirmed.

Exclusion Criteria

My brain or spinal cord cancer is stable without needing steroids.

I have or had an autoimmune or inflammatory disorder.

I do not have active infections like TB, hepatitis B, hepatitis C, or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab + tremelimumab combination therapy + SoC chemotherapy, durvalumab monotherapy + SoC chemotherapy, or SoC chemotherapy alone

Approximately 25 months

Tumor scans at baseline, Week 6, Week 12, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 8 weeks until second progression/death

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abraxane + carboplatin
• Durvalumab
• Gemcitabine + carboplatin
• Gemcitabine + cisplatin
• Pemetrexed + carboplatin
• Pemetrexed + cisplatin
• Tremelimumab

Trial Overview The study compares three treatments: Durvalumab plus Tremelimumab with standard chemotherapy, Durvalumab with standard chemotherapy alone versus just the standard chemo. It's a Phase III trial to see which combination works best as a first line treatment for advanced lung cancer without specific genetic changes.

How Is the Trial Designed?

Group I: Treatment Arm 2 Experimental Treatment 6 Interventions

durvalumab monotherapy + SoC chemotherapy

Group II: Treatment Arm 1 Experimental Treatment 7 Interventions

durvalumab + tremelimumab combination therapy + SoC chemotherapy

Group III: Treatment Arm 3 Active Control 5 Interventions

SoC chemotherapy alone

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

The phase III POSEIDON trial demonstrated that a three-drug regimen combining the CTLA4 inhibitor tremelimumab, the PD-L1 inhibitor durvalumab, and chemotherapy significantly improves progression-free survival and overall survival in patients with metastatic non-small cell lung cancer compared to chemotherapy alone.

This study suggests that targeting multiple immune pathways with this combination therapy may enhance treatment effectiveness for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Drug Regimen Bests Chemo in NSCLC. [2022]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In a phase Ib study involving 136 patients, durvalumab (Du) combined with tremelimumab (Tr) and standard platinum-doublet chemotherapy was found to be safe, with most drug-related adverse events being mild (≤ grade 2) and primarily due to chemotherapy.

Among 73 patients with non-small cell lung cancer (NSCLC), the treatment achieved a 51% objective response rate, with a median progression-free survival of 6.5 months and overall survival of 19.8 months, indicating promising efficacy comparable to other immunotherapy and chemotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Juergens, RA., Hao, D., Ellis, PM., et al.[2021]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

In the phase III CASPIAN study, the combination of durvalumab with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer compared to etoposide plus platinum alone.

Patient-reported outcomes showed that the addition of durvalumab not only maintained quality of life but also delayed the worsening of key symptoms like appetite loss, cough, and fatigue, indicating a beneficial impact on patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Goldman, JW., Garassino, MC., Chen, Y., et al.[2021]

In the phase III CASPIAN trial involving previously untreated adults with extensive-stage small cell lung cancer (ES-SCLC), the addition of durvalumab to chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Durvalumab combined with etoposide and either carboplatin or cisplatin demonstrated a manageable safety profile, making it a valuable first-line treatment option and an accepted standard of care for patients with ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. Al-Salama, ZT.[2022]

In the phase III CASPIAN study, durvalumab combined with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer, with a median overall survival of 12.9 months compared to 10.5 months for the control group.

After more than 3 years of follow-up, durvalumab plus etoposide showed a 36-month overall survival rate of 17.6%, indicating that this combination is a promising first-line treatment option for extensive-stage small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. Paz-Ares, L., Chen, Y., Reinmuth, N., et al.[2022]

Citations

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215TiP A phase II study of durvalumab (MEDI 4736) ... DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance specifically in frail LD-SCLC pts who have not progressed following concomitant or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

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A phase II study of durvalumab (MEDI4736) immediately ... Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709937

Durvalumab after Chemoradiotherapy in Stage III Non– ... The 12-month progression-free survival rate was 55.9% (95% CI, 51.0 to 60.4) with durvalumab and 35.3% (95% CI, 29.0 to 41.7) with placebo, and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02352948

NCT02352948 | A Global Study to Assess the Effects ... This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in ...

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A Global Study to Assess the Effects of MEDI4736 ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

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A Phase III Study of Durvalumab (MEDI4736) With or ... A global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus ...